Process for the production of 2,3,5-trimethylhydroquinone diesters

Abstract

The invention relates to an improved process for the production of 2,3,5-trimethylhydroquinone diesters by rearrangement of 2,6,6-trimethyl-2-cyclohexene-1,4-dione (4-oxoisophorone, ketoisophorone) in the presence of a dissolved, acidic catalyst and an acylating agent, such as for example carboxylic anhydrides or carboxylic acid halides. The 2,3,5-trimethylhydroquinone diester can optionally then be saponified to give free 2,3,5-trimethylhydroquinone (TMHQ), which is a valuable building block in the synthesis of vitamin E.

What is claimed is:  
     
       1. A process for the production of trimethylhydroquinone diesters of the formula                    
       wherein R and R 1  may be identical or different moieties, and represent an optionally substituted aliphatic, alicyclic C 1  to C 20  group,  
       comprising reacting 2,6,6-trimethyl-2-cyclohexene-1,4-dione(ketoisophorone or KIP)                    
       with an acylating agent in the presence of an acidic catalyst system comprising catalytic quantities of a protonic acid to form a trimethylhydroquinone diester, 
       wherein the protonic acid comprises at least one boron-containing member selected from the group consisting of orthoboric acid, boron oxide and boric acid triester and at least one carboxylic acid selected from the group consisting of hydroxycarboxylic acids, dicarboxylic acids and tricarboxylic acids, which optionally may also contain hydroxy groups.  
     
     
       2. The process according to  claim 1 , wherein the at least one carboxylic acid is a dicarboxylic acid of general formula 
        HO 2 C—R 3 —CO 2 H  (II) 
       wherein R 3  represents a member selected from the group consisting of an aryl group, (CH 2 ) m , and (CH 2 ) m (CHX) r ,  
       wherein m represents an integer from 0 to 20, r represents an integer from 1 to 5 and X represents OH, H, (CH 2 ) P —(CX)(COOH)—(CH 2 ) P , or a C 2 -C 6  alkenyl group and  
       wherein  P  represents a number from 1 to 3.  
     
     
       3. The process according to  claim 2 , wherein R 3  is a member selected from the group consisting of phenylene, naphthylene and (CH 2 ) m . 
     
     
       4. The process according to  claim 2 , wherein R 3  is (CH 2 ) m  or (CH 2 ) m (CHX) r  and m represents an integer from 0 to 4. 
     
     
       5. The process according to  claim 1 , wherein the at least one carboxylic acid comprises a hydroxy acid of general formula 
       
         
           R 2 —CO 2 H  (I)  
         
       
       wherein 
       R 2  represents an aryl compound substituted by at least one member selected from the group consisting of OH, HO—(CH 2 ) q , and CH 3 (CHOH) n (CH 2 ) m —, wherein  
       m represents an integer from 0 to 20,  
       n represents an integer from 1 to 5, and  
       q represents an integer from 1 to 6.  
     
     
       6. The process according to  claim 5 , wherein m represents an integer from 0 to 8. 
     
     
       7. The process according to  claim 5 , wherein n represents an integer from 1 to 4. 
     
     
       8. The process according to  claim 1 , wherein the at least one carboxylic acid comprises a hydroxyl group-containing amino acid. 
     
     
       9. The process according to  claim 8 , wherein the amino acid is serine or threonine. 
     
     
       10. The process according to  claim 1 , wherein the acidic catalyst system comprises a mixture of orthoboric acid and oxalic acid or salicylic acid. 
     
     
       11. The process according to  claim 1 , wherein the acidic catalyst system comprises a mixture of orthoboric acid and a member selected from the group consisting of oxalic acid, salicylic acid, tartaric acid and citric acid, in a molar ratio of 1:1 to 1:10. 
     
     
       12. The process according to  claim 11 , wherein the molar ratio is 1:2 to 1:5. 
     
     
       13. The process according to  claim 1 , wherein the acidic catalyst system comprises a mixture of one or more of the boron-containing members and one or more of the carboxylic acids in a quantity of 0.1 to 10 mole % based on the ketoisophorone used. 
     
     
       14. The process according to  claim 1 , wherein the acylating agent comprises an acylating agent of general formula                    
       wherein: 
       R, R 1 , are the same or different and represent an optionally substituted, aliphatic, alicyclic C 1  to C 20  group, or an aryl group.  
     
     
       15. The process according to  claim 14 , wherein the aliphatic group is a C 2  to C 4  aliphatic group. 
     
     
       16. The process according to  claim 14 , wherein the aryl group is a phenylene group. 
     
     
       17. The process according to  claim 1 , further comprising 
       optionally removing unreacted carboxylic acid anhydride and carboxylic acid by distillation, and  
       saponifying the trimethylhydroquinone diester without previous isolation, by adding at least one member selected from the group consisting of water and dilute acid, thereby forming trimethylhydroquinone.  
     
     
       18. The process according to  claim 17 , further comprising isolating the trimethylhydroquinone. 
     
     
       19. The process according to  claim 14 , wherein the acylating agent comprises a carboxylic acid chloride. 
     
     
       20. The process according to  claim 1 , wherein the at least one carboxylic acid comprises a compound of general formula (I) 
       
         
           R 2 —CO 2 H  (I)  
         
       
       wherein 
       R 2  represents an aryl compound substituted by at least one member selected from the group consisting of OH, HO—(CH 2 ) q , and CH 3 (CHOH) n (CH 2 ) m —, wherein  
       m represents an integer from 0 to 20,  
       n represents an integer from 1 to 5, and  
       q represents an integer from 1 to 6;  
       and a compound of general formula (II) 
       
         
           HO 2 C—R 3 —CO 2 H  (II)  
         
       
       wherein R 3  represents a member selected from the group consisting of an aryl group, (CH 2 ) m , and (CH 2 ) m (CHX) r ,  
       wherein m represents an integer from 0 to 20, r represents an integer from 1 to 5 and X represents OH, H, (CH 2 ) P —(CX)(COOH)—(CH 2 ) P , or a C 2 -C 6  alkenyl group and  
       wherein  P  represents a number from 1 to 3.  
     
     
       21. The process according to  claim 1 , further comprising: 
       continuously separating catalytically active acids of the acidic catalyst system by extraction with a polar solvent, and  
       reprocessing the catalytically active acids for re-use.